title: Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease.
abstract: BACKGROUND
  Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients.
  
  
  METHODS
  We performed a cross-sectional study of 149 adult patients followed between 2000 and 2011 in a comprehensive sickle cell clinic. All patients were assessed for albuminuria either by direct measurement or by urinary chemical strip (dipstick) testing. Urinary albumin-to-creatinine ratios (UACRs) were available for 112 patients. Hydroxyurea exposure was defined as ≥3 months of therapy before the assessment of albuminuria. Albuminuria was defined as either UACR ≥30 mg/g or ≥1+ proteinuria on two separate dipsticks. We constructed a multivariate logistic regression model to assess the association between hydroxyurea and albuminuria.
  
  
  RESULTS
  The prevalence of albuminuria was lower among patients on hydroxyurea (34.7 versus 55.4%; P = 0.01) as was median albumin excretion (17.9 versus 40.5 mg/g; P = 0.04). In multivariate analysis, hydroxyurea was associated with a lower likelihood of albuminuria (odds ratio 0.28, 95% CI: 0.11-0.75, P = 0.01), adjusting for age, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, tricuspid regurgitant jet velocity, hypertension and acute chest syndrome.
  
  
  CONCLUSIONS
  In our population of sickle cell patients, those using hydroxyurea were less than one-third as likely to exhibit albuminuria. Hydroxyurea use may prevent development of overt nephropathy or the progression of sickle cell disease nephropathy to end-stage renal disease, and its use for this indication merits further investigation.
authors.affiliation: UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Laurin
authors.affiliation: UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Nachman
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Payal C
authors.initials: PC
authors.lastname: Desai
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Ataga
authors.affiliation: UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Vimal K
authors.initials: VK
authors.lastname: Derebail
mesh_terms: D056586:Acute Chest Syndrome / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology; D000755:Anemia, Sickle Cell / Q000453:epidemiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000986:Antisickling Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D015995:Prevalence; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000986:Antisickling Agents; D006918:Hydroxyurea
keywords: albuminuria; chronic kidney disease; hydroxyurea; nephropathy; sickle cell